ArticleScientific reports2015
Mechanism of action of thalassospiramides, a new class of calpain inhibitors.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- Pooled it
- Industrial and Pharmaceutical Applications of Microbial Diversity of Hypersaline Ecology from Lonar Soda Crater.Current pharmaceutical biotechnology · 2024Review
- A Survey of Didemnin Depsipeptide Production inMarine drugs · 2023Article
- Calpains, the proteases of two faces controlling the epithelial homeostasis in mammary gland.Frontiers in cell and developmental biology · 2023Review
- Targeting eukaryotic proteases for natural products-based drug development.Natural product reports · 2020Review
- Pass-back chain extension expands multimodular assembly line biosynthesis.Nature chemical biology · 2020Article
- Investigating the Biosynthesis of Natural Products from Marine Proteobacteria: A Survey of Molecules and Strategies.Marine drugs · 2017Review
- Covalent Modifiers: A Chemical Perspective on the Reactivity of α,β-Unsaturated Carbonyls with Thiols via Hetero-Michael Addition Reactions.Journal of medicinal chemistry · 2017Article
- Chinese Herbal Medicine Meets Biological Networks of Complex Diseases: A Computational Perspective.Evidence-based complementary and alternative medicine : eCAM · 2017Review
- Family-wide Structural Characterization and Genomic Comparisons Decode the Diversity-oriented Biosynthesis of Thalassospiramides by Marine Proteobacteria.The Journal of biological chemistry · 2016Article
- Gene/protein expression of CAPN1/2-CAST system members is associated with ERK1/2 kinases activity as well as progression and clinical outcome in human laryngeal cancer.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Thalassospiramides comprise a large family of lipopeptide natural products produced by Thalassospira and Tistrella marine bacteria. Here we provide further evidence of their nanomolar inhibitory activity against the human calpain 1 protease. Analysis of structure-activity relationship data supported our hypothesis that the rigid 12-membered ring containing an α,β-unsaturated carbonyl moiety is the pharmacologically active functional group, in contrast to classic electrophilic "warheads" in known calpain inhibitors. Using a combination of chemical modifications, mass spectrometric techniques, site-directed mutagenesis, and molecular modeling, we show the covalent binding of thalassospiramide's α,β-unsaturated carbonyl moiety to the thiol group of calpain's catalytic Cys115 residue by a Michael 1,4-addition reaction. As nanomolar calpain inhibitors with promising selectivity and low toxicity from natural sources are rare, we consider thalassospiramides as promising drug leads.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.